PKU watch - case study
between 500-600µmol/l, so that any reductions in blood phenylalanine produced by sapropterin could be clearly seen and assessed.
He was given a once daily dose of 10mg/kg/day sap-
ropterin for four weeks. He was a slow sapropterin respond- er and it was not until day five that his blood phenylalanine concentrations reduced by 40 percent. However, for the rest of the four-week trial, all phenylalanine concentra- tions were below 350µmol/l and there was little daily blood phenylalanine fluctuation. His phenylalanine tolerance in- creased from 9g/daily to 20g/daily. This enabled him to eat ‘normal’ toast with his friends and he was also more likely to sit with the rest of the family for meals. He had neuro-pyschometric testing pre- and four weeks post-sapropterin. This boy reported himself to be ‘calmer,’ ‘less hyper’ and socially ‘more normal’. His self- esteem improved and his carer reported positive mood changes: he was happier, more relaxed, no longer an ‘angry, young man’. Improvements in attention and con- centration were also reflected both at home and school. On repeat neuro-psychometric testing only four weeks post-sapropterin, there were subtle improvements across indices of attention measures, speed of inhibition and switching and immediate memory span. His energy intake increased from 1,600kcal/d to 2,200 kcal/d and his weight also improved. In the short term, sapropterin therapy appeared to
result in subtle improvements in attention, executive function, mood and nutritional status in a previously well- controlled boy with PKU. The case study is delighted with his diet and the boy has no desire to return to life without sapropterin.
Conclusions
In PKU, the introduction of sapropterin is a welcome adjunct to diet therapy in the treatment of BH4 responsive PKU patients who have issues with their low phenylalanine diet or who are unable to maintain their plasma phenyla- lanine concentration within target ranges by diet therapy alone. However, there are many unanswered questions that require addressing. Further longitudinal, controlled studies are required to study neurocognitive changes with saprop- terin. Studies are also necessary to determine nutritional ad- equacy, growth, blood phenylalanine control during illness and longer-term compliance and safety with sapropterin. However, sapropterin is likely to relax dietary treatment for many patients and potentially improve their quality of life.
References 1 Blau N, Belanger-Quintana A, Demirkol M, Feillet F, Giovannini M, Macdonald A, et al. Optimizing the use of sapropterin (BH(4)) in the management of phenylketonuria. Mol Genet Metab 2009; 96:158-163 2 Christ SE, Huijbregts SC, de Sonneville LM, White DA. Executive function in early-treated phe- nylketonuria: profile and underlying mechanisms. Mol Genet Metab. 2010; 99 Suppl 1:S22-32 3 Humphrey M, Francis I, Upton H, Nation J, Boneh A. Effect of BH4 on phe/tyr ratio and fluc- tuations in phe levels in BH4 responsiveness PKU patients. Molecular Genetics and Metabolism. 2009, 98, p 25. Abstract 194 4 Janzen D, Nguyen M. (2010) Beyond executive function: non-executive cognitive abilities in individuals with PKU. Mol Genet Metab. 99 Suppl 1:S47-51 5 Kure S, Hou DC, Ohura T, Iwamoto H, Suzuki S, Sugiyama N, Sakamoto O, Fujii K, Matsubara Y, Narisawa K. Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. J Pediatr. 1999; 135: 375-8 6 Levy HL, Milanowski A, Chakrapani A, Cleary M, Lee P, Trefz FK, Whitley CB, Feillet F, Feigen- baum AS, Bebchuk JD, Christ-Schmidt H, Dorenbaum A, for the Sapropterin Research Group. Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of pheny- lalanine concentration in patients with phenylketonuria: a phase III randomised placebo- controlled study. Lancet 370 [9586] (2007) 504–510 7 Trefz FK, Burton B, Longo N, Martinez-Pardo Casanova M, Gruskin DJ, Dorenbaum A, Kakkis ED, Crombez EA, Grange DK, Harmatz P, Lipson MH, Milanowski A, Randolph LM, Vockley J, Whitley CB, Wolff JA, Bebchuk J, Christ-Schmidt H, Hennermann J for the Sapropterin Study Group. Efficacy of sapropterin dihydrochloride in increasing phenylalanine tolerance in chil- dren with phenylketonuria: A Phase III, randomized, double-blind, placebo-controlled study. J. Pediatr. 154 (2009) 700–707 8 Trefz FK, Scheible D, Frauendienst-Egger G, Korall H, Blau N. Long-term treatment of patients with mild and classical phenylketonuria by tetrahydrobiopterin. Mol Genet Metab. 2005 Dec;86 Suppl 1:S75-80. Epub 2005 Oct 20
Help your
patients take a bite out of life
Kuvan 100 mg soluble tablets Sapropterin dihydrochloride
Indications Treatment of hyperphenylalaninaemia (HPA) in adult and paediatric patients of 4 years of age and over with phenylketonuria (PKU) who have been shown to be responsive to such treatment. Treatment of hyperphenylalaninaemia (HPA) in adult and paediatric patients with tetrahydrobiopterin (BH4) deficiency who have been shown to be responsive to such treatment
Prescribers should consult the Summary of Product Characteristics before prescribing, particularly in relation to side-effects, precautions and contra-indications
Legal category POM
Marketing Authorisation Holder Merck KGaA Frankfurter
Str. 250 64293 Darmstadt Germany
Name and Address of Distributor in UK Merck Serono Ltd,
Bedfont Cross, Stanwell Road, Feltham, Middlesex, TW14 8NX Tel: +44 (0)20 8818 7200
Adverse events should be reported. Reporting forms and information can be found at
www.yellowcard.gov.uk. In the Republic of Ireland information can be found at
www.imb.ie. Adverse events should also be reported to Merck Serono Limited - Tel: +44 (0)20 8818 7373 or email:
medinfo.uk@
merckserono.net.
Date of Preparation: July 2009
32
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Job Number: KUV09-0085
NHDmag.com June '10 - issue 55
21/07/2009 10:09
Name and Address of Distributor in Ireland Merck Serono,
3013 Lake Drive, Citywest Business Campus, Dublin 24 Tel: + 353 (0)1 4661910
Further information is available on request from the marketing authorisation holder or may be found in the Summary of Product Characteristics
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